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Familial Cancer
Published in: Familial Cancer 1/2015

01-03-2015 | Original Article

Estimate of the penetrance of BRCA mutation and the COS software for the assessment of BRCA mutation probability

Authors: Jacopo Berrino, Franco Berrino, Silvia Francisci, Bernard Peissel, Jacopo Azzollini, Valeria Pensotti, Paolo Radice, Patrizia Pasanisi, Siranoush Manoukian

Published in: Familial Cancer | Issue 1/2015

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Abstract

We have designed the user-friendly COS software with the intent to improve estimation of the probability of a family carrying a deleterious BRCA gene mutation. The COS software is similar to the widely-used Bayesian-based BRCAPRO software, but it incorporates improved assumptions on cancer incidence in women with and without a deleterious mutation, takes into account relatives up to the fourth degree and allows researchers to consider an hypothetical third gene or a polygenic model of inheritance. Since breast cancer incidence and penetrance increase over generations, we estimated birth-cohort-specific incidence and penetrance curves. We estimated breast and ovarian cancer penetrance in 384 BRCA1 and 229 BRCA2 mutated families. We tested the COS performance in 436 Italian breast/ovarian cancer families including 79 with BRCA1 and 27 with BRCA2 mutations. The area under receiver operator curve (AUROC) was 84.4 %. The best probability threshold for offering the test was 22.9 %, with sensitivity 80.2 % and specificity 80.3 %. Notwithstanding very different assumptions, COS results were similar to BRCAPRO v6.0.
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Metadata
Title
Estimate of the penetrance of BRCA mutation and the COS software for the assessment of BRCA mutation probability
Authors
Jacopo Berrino
Franco Berrino
Silvia Francisci
Bernard Peissel
Jacopo Azzollini
Valeria Pensotti
Paolo Radice
Patrizia Pasanisi
Siranoush Manoukian
Publication date
01-03-2015
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 1/2015
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-014-9766-8

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